Abstract：
:Steroids possessing an ethynyl group at position 17α (tertiary alcohols) are well known to be more stable than their non-ethynyl analogs (secondary alcohols). To facilitate the development of new drugs with better metabolic stability, we developed a new diethylsilyl acetylenic linker allowing us to rapidly synthesize libraries of ethynylated steroid derivatives using a solid-phase strategy. To illustrate its usefulness, this linker was used to expand the molecular diversity of a lead compound having a hydroxy acetylenic pattern and to potentially find new compounds with interesting cytotoxic activity against leukemia cell lines. Herein, we report the chemical synthesis and the characterization of three libraries of ethynylated aminosteroid derivatives using the diethylacetylenic linker. We discuss their antiproliferative activities obtained in 2 leukemia cell lines (HL-60 and Jurkat), which results provided new structure-activity relationships. We also identified a new promising aminosteroid derivative with an azetidine moiety (compound B1) inhibiting 60% and 75% of HL-60 and Jurkat cell proliferation, respectively, at 1 μM. More generally, these results validate the use of a diethylsilyl acetylenic linker for researchers interested in generating libraries of alcohol derivatives with better stability and drug profile.
journal_name
Steroidsjournal_title
Steroidsauthors
Talbot A,Maltais R,Kenmogne LC,Roy J,Poirier Ddoi
10.1016/j.steroids.2015.12.019subject
Has Abstractpub_date
2016-03-01 00:00:00pages
55-64eissn
0039-128Xissn
1878-5867pii
S0039-128X(15)00325-6journal_volume
107pub_type
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